The objective of this project is to design, construct and test a fiber optic catheter to obtain confocal reflected light images of human epithelial tissues in vivo with several micron resolution in near real time. The intended application of the device is to aid in the diagnosis, and potentially screening, of epithelial pre-cancers. To demonstrate the potential clinical advantages of fiber-optic confocal imaging, we will assess the capability of our device to measure tissue morphology in vivo to aid in the recognition of pre-cancers of the uterine cervix and oral mucosa. We believe that successful completion of this project will provide a clinical tool which could dramatically improve recognition and monitoring of epithelial precancers of the oral mucosa, uterine cervix, urinary bladder, colon, and other organs with high incidences of epithelial cancer. We have designed and tested a prototype of this device which uses a single optical fiber and commercially available, macroscopic optical components. However, to achieve images at near video rate through an endoscope, a small, multi-fiber device which can scan the entire epithelial thickness is required. Our preliminary results indicate that such a device is feasible. The goal of the proposal is to design, construct and test three multi-fiber prototypes to address the three major engineering advances required to achieve near viedeo rate images of the entire epithelial thickness with micron resolution. The specific aims of the project to: (1) design a multi-fiber confocal system (prototype1) which uses commercially available macroscopic optics to obtain images from a 75-150 mu diameter field of view with 2-3 mu lateral resolution and 5-7 mu axial resolution in 1 second from a single focal plane depth, parallel to the tissue surface, located approximately 200 mu beneath the tissue surface, (2) to construct, and test this system using phantoms, the oral mucosa of normal volunteers, and normal and pre-cancerous cervial epithelium in a pilot study of 10 patients ith cervical intra-epithelial neoplasia (CN), (3) to study methods of contrast enhancement in vivo, (4) to design and test a 1 cm outer diameter assembly of commercially available lenses to be used with prototype 1; however, in prototype 2, the tissue plane to be imaged will not be parallel to the tissue surface, but will form a small angle with the surface so that the cells in the image plane range from the surface of the epithelium to the basement membrane, and (5) to design a third prototype, which will use custom optics so that the outer diameter of the distal section is no greater than 3 mm and it can be used in conjuction with standard endoscopy equipment to access sites other than the oral mucosa and uterine cervix.